KR101278106B1 - The preparation method of cellulose type polymer antimicrobial using ionic liquid - Google Patents

Abstract

The present invention relates to a method for producing a cellulose-based fixed polymer antimicrobial agent having a functional group having an antimicrobial function by using an ionic liquid. More specifically, after dissolving cellulose using an ionic liquid, quaternary alkylammonium salts, quaternary alkylphosphoronium salts, 5-chloro-8-quinolinyl, triclosan, chlorohydrodantoin, etc. having antibacterial functions are bound to the cellulose polymer. The present invention relates to a method for preparing a fixed polymer antimicrobial agent of Formula 1 above.

Description

The preparation method of cellulose type polymer antimicrobial using ionic liquid}

The present invention relates to a method for producing a cellulose-based fixed polymer antimicrobial agent having a functional group having an antimicrobial function by using an ionic liquid. In more detail, after dissolving cellulose using an ionic liquid, quaternary alkyl ammonium salt, quaternary alkyl phosphonium salt, 5-chloro-8-quinolinyl, triclosan, chlorohydantoin and the like having antibacterial function are bound to the cellulose polymer. The present invention relates to a method for preparing a fixed polymer antimicrobial agent.

Ionic liquids are environmentally friendly solvents with physicochemical properties such as low melting point, good solubility. Non-derivative cellulose solutions, a category of ionic liquids, have recently been studied in the field of cellulose. However, cellulose is a compound having high crystallinity and strong intermolecular and intramolecular hydrogen bonds, so that it is not dissolved in water or a general solvent. Therefore, cellulose has many limitations for their development and application. Cellulose was reported in 2002 by Roger et al. [RP Swatloski, SK Spear, JD Holbrey, RD Rogers, J. Am. Chem. Soc. 124 (18) (2002) 4974 found that cellulose could be dissolved in 1-butyl-3-methylimidazolium chloride ([C ₄ mim] Cl, [BMIM] Cl), an ionic liquid. It opened a new chapter on technology. In the room temperature ionic liquid only jigiman only moistened to the cellulose fiber naeteumyeo out that the complete dissolution does sikijineun, when heated to ^{100 ~110 ℃ Cl -, Br -} , SCN - in the ionic liquid with an anion such as It was found that it could dissolve slowly. Len et al. [Q. Ren, J. Wu, J. Zhang, JS He, ML Guo, Aeta Polym. Siniea 3 (3) (2003) 448 J. Wu, J. Zhang, H. Zhang, J. He, Q. Ren, M. Guo, Biomacromolecules 5 (2) (2004) 266 are ionic liquids 1-allyl. It was found that -3-methylimidazolium chloride ([Amim] Cl) had good properties for dissolving cellulose. Alkaline activated cellulose (DP = 640) was added to [Amim] Cl at 80 ° C. and stirred to obtain a 5% cellulose solution. The solubility of cellulose depends on the length of the side chains, such as allyl, ethyl, butyl and octyl. The maximum solubility was obtained in C4 butyl [L. Feng, Z.-l. Chen, J. Mol. Liq. 2008, 142, 1], The double bond (allyl) is known to lower the viscosity of the ionic liquid.

[G. Laus, G. Bentivoglio, H. Schottenberger, V. Kahlenberg, H. Kopacka, H. Roeder, T. Roeder, H. Sixta, Lenzinger Ber. 2005, 84, 71 A. J. Carmichael, M. Deetlefs, M. J. Earle, U. Frohlich, K. R. Seddon, Ionic liquids: Improved syntheses and new products. In Ionic Liquids as Green Solvents: Progress and Prospects American Chemical Society: Washington, DC, 2003; Vol. 856, pp 14-31. In addition, ionic liquids with an even number of carbons in the side chain of the carbon chain between C2 and C20 showed higher cellulose dissolving power than ionic liquids having an odd number of carbons [T. Erdmenger, C. Haensch, R. Hoogenboom, U. S. Schubert, Macromol. Biosci. 2007, 7, 440.

For several centuries, several antimicrobial polymers have been synthesized by immobilizing low molecular weight antimicrobial agents on the polymer. Compared with conventional low molecular weight antimicrobial agents, antimicrobial polymers have the advantages of improved antimicrobial activity, reduced residual toxicity, increased antimicrobial activity and selectivity, and longer lifespan. Antimicrobial polymers have been used as coatings in many fields, such as food processing, filtration, and medical devices. It has also been used as a preservative for the garment industry, fungicides and pharmaceuticals made of antibacterial fibers. Some commonly used low molecular weight antimicrobials are fluoroquinoline, quaternary ammonium salts, phosphonium salts, and the like. Among these antibacterial agents, quaternary ammonium compounds are most widely used.

Quaternary ammonium compounds have the advantages of excellent cell membrane permeability, low toxicity, environmental stability, low skin irritation, low corrosiveness, and extended residence time and bioactivity compared to other antimicrobial agents. A common property of quaternary ammonium compounds is that they have both positive charges and hydrophobic segments. Quaternary ammonium compounds with long alkyl chains have the ability to work with cell membranes to kill microbes such as bacteria, fungi, and fungi. It is generally accepted that positively charged quaternary ammonium compounds are adsorbed by electrostatic interactions on negatively charged cell surfaces, and that long lipophilic chains promote diffusion across cell walls. In particular, long chains along the polymer chain can damage the plasma membrane or reduce the plasma composition, resulting in the death of microorganisms. The antimicrobial activity of quaternary ammonium compounds depends greatly on the overall molecular structure and the length of the alkyl chain. Increasing the alkyl chain length of an amphiphilic compound, such as a 14 carbon alkyl chain, has been reported to increase antimicrobial activity against both Gram negative and Gram positive [T. Abel, J. I. Cohen, R. Engel, M. Filshtinskaya, A. Melkonian, K. Melkonian, Carbohydr. Res., 337 (2002) 2495 J. D. Schroeder, J. C. Scales, U.S. Patent 20020051754, 2002 C. R. Birnie, D. Malamud, R. L. Schanaare, Antimicrob. Agents Chemother., 44 (2000) 2514. There are two approaches to attaching these antimicrobials to polymers [T. Tashiro, Macromol. Mater. Eng., 286 (2001) 63]. The first is to introduce an antimicrobial agent into the monomer and then polymerize. This method has the advantage that various other monomers can be copolymerized and the composition can be easily changed. The second method is to combine an antimicrobial agent with a preformed functional polymer. This method has the advantage of converting the functional polymer into other antimicrobial agents and controlling the degree of conversion.

In order to solve the above problems, an object of the present invention is to directly replace in the state of completely dissolving cellulose using an ionic liquid can replace all of the remaining hydroxyl groups that do not have antimicrobial activity can increase the antimicrobial activity, and Since the cellulose polymer is immobilized by being introduced as a functional group, the present invention provides a method for preparing a fixed polymer antimicrobial agent having high antimicrobial activity and selectivity, as well as reduced residual toxicity and longer life.

In order to achieve the above object, a cellulose dissolved using an ionic liquid was prepared by a method of synthesizing the compound represented by the following Structural Formula 1. The ionic liquid used in the present invention is [Amim] Cl [H. Zhang, J. Wu, J. Zhang, and J. He, Macrmolecules 38 (2005) 8272-8277], [Bmim] Cl [J. G. Huddleston, A. E. Visser, W. M. Reichert, H. D. Willauer, G. A. Broker and R. D. Rogers, Green Chemistry, 2001, 3, 156-164], and [Omim] Cl [S. Liu, C. Xie, S. Yu, F. Liu, Catalysis Comm. 10 (2009) 986-988] was synthesized by known methods.

[Structural formula 1]

Where AM ₁ , AM ₂ , and AM ₃ are each independently

,

,

,

,

그리고 적어도 하나의

을 나타낸다

,

,

,

,

And at least one

Indicates

R ₁ , R ₂ , and R ₃ each independently represent an alkyl group.

R ₄ and R ₅ independently represent a hydrogen atom or a methyl group

, 또는

를 나타낸다R ₆ is

, or

Indicates

R ₇ represents a hydrogen atom or a methyl group

The compound represented by Structural Formula 1 has quaternary ammonium base, quaternary phosphonium base, and chlorohydantoin group having antibacterial properties in the cellulose polymer main chain.

The compound represented by formula 1 can be synthesized by known methods. For example, the cellulose represented by Structural Formula 2 dissolved in an ionic liquid in Scheme 1 is then acetylated with chloroacetyl chloride added with pyridine to synthesize an intermediate as shown in Structural Formula 3, and then dissolved in an ionic liquid. The intermediate producing compound of formula 3 can be separated by washing the ionic liquid by adding water. The isolated intermediate product of formula 3 can then be reacted with trialkylamine or trialkylphosphine to synthesize the final product of formula 1. In addition, by reacting hydantoin and calcium hydroxide in a dimethylacetamide solution with an isolated intermediate product such as the structural formula 3 of the following scheme 1 to synthesize a second intermediate such as the structural formula 4, hypochlorous acid, acetic acid and TBAC can be reacted to synthesize the compound of formula 1 as a product.

[Reaction Scheme 1]

1 is a manufacturing process of the polymer antimicrobial agent according to an embodiment of the present invention.

As described above, the present invention using the ionic liquid is a method of directly reacting in a completely dissolved state of cellulose, so that all of the remaining hydroxyl groups having no antimicrobial activity can be substituted, thereby increasing antimicrobial activity.

In addition, the present invention using the ionic liquid can be made of various types of biological resources such as wood-based biomass as a raw material can reduce the raw material cost.

In addition, since the antimicrobial agent of the present invention is immobilized by introducing a functional group into the cellulose polymer, it can be used in many fields such as food processing, filtration, and medical devices with high antimicrobial activity and selectivity as well as reduced residual toxicity and longer lifespan. It is also applicable to many applications, such as the textile garment industry, disinfectants and preservatives.

1 is a manufacturing process of the polymer antimicrobial agent according to a preferred embodiment.

Preferred implementations of the invention are as described below.

I. Dissolution of Cellulose with Ionic Liquid

Since BKP and Avicel samples did not differ in dissolution time depending on whether or not they were dried, they were used as received in all the following procedures. BKP is in the form of a paper. The BKP is ground and absorbed as much as possible to the ionic liquid to make it melt like heating. Avicel was used as it is as a white fine horizontal form. Ionic liquids ([Amim] Cl, [Bmim] Cl, [Omim] Cl, and [C2mm] (MeO) ₂ PO ₂ ) were added to the vial and heated, followed by addition of cellulose samples. (50 mg, 5 wt%). The sample was stirred until it melted into one phase.

Experimental Example 1

15 g of the ionic liquid was placed in a vial and heated at 60 ° C. for 5 minutes, then 1.5 g of Avicel was added and heated at 50 ° C. for 60 minutes with stirring. As a result of heating, Avicle was not dissolved at all.

Experimental Example 2

15 g of the ionic liquid was placed in a vial and heated at 60 ° C. for 5 minutes, then 1.5 g of Avicel was added and heated at 75 ° C. for 60 minutes with stirring. As a result of heating, Avicle began to slowly melt in all ionic liquids, but it was not completely dissolved, but the melting change was found to be yuan.

Experimental Example 3

After putting 2 g of the ionic liquid into the vial and heating at 60 ° C. for 5 minutes, 0.1 g of Avicel was added and heated at 100 ° C. for 60 minutes with stirring. The heating resulted in the complete dissolution of Avicle in all ionic liquids as a transparent phase.

Experimental Example 4

10 g of the ionic liquid was placed in a vial and heated at 60 ° C. for 5 minutes, and 0.5 g of Avicel was added thereto and heated at 100 ° C. for 180 minutes with stirring. As a result of heating, the color of the solution was slightly changed in the case of [Bmim] Cl, but in all the ionic liquids, Avicle was completely dissolved and appeared as a transparent phase.

Experimental Example 5

10 g of the ionic liquid was placed in a vial and heated at 60 ° C. for 5 minutes, and 0.5 g of Avicel was added thereto and heated at 100 ° C. for 180 minutes with stirring. As a result of heating, the solution became turbid and black except for [C2mm] (MeO) ₂ PO ₂ ).

Comparative Example 1

15 g of the ionic liquid was placed in a vial and heated at 60 ° C. for 5 minutes, and 1.5 g of Avicel was added thereto, followed by heating at room temperature for 60 minutes while stirring. As a result of heating, it did not melt at all in its initial state.

Experimental Example 6

After putting 2 g of the ionic liquid into the vial and heating at 60 ° C. for 5 minutes, 0.1 g of BKP was added thereto and heated at 100 ° C. for 180 minutes while stirring. As a result of heating, the color of the solution was slightly changed in the case of [Bmim] Cl.

Comparative Example 2

15 g of the ionic liquid was placed in a vial and heated at 60 ° C. for 5 minutes, and then 1.5 g of BKP was added thereto, followed by heating at room temperature for 60 minutes with stirring. As a result of heating, it did not melt at all in its initial state.

Comparative Example 2

15 g of the ionic liquid was placed in a vial and heated at 60 ° C. for 5 minutes, and then 1.5 g of BKP was added thereto, followed by heating at room temperature for 60 minutes with stirring. As a result of heating, it did not melt at all in its initial state.

II. Separation and Extraction of Cellulose Dissolved in Ionic Liquids

After heating, distilled water was poured into one phase solution, depending on the type of ionic liquid, separation or presence of a turbid liquid.

The solution was washed with water and acetone and filtered through a glass filter. The filtered cellulose product was separated by drying at 70 ° C. for at least 2 days.

Experimental Example 7

Add 10 mL of distilled water to the solution of Avicel in the ionic liquid and mix it as much as possible using Voltex with sufficient agitation. If left for about 1 hour, the white substance sinks or remains in a cloudy state depending on the type of ionic liquid. do. The resulting material was filtered through a glass filter, washed several times with water and acetone, and dried in a dryer. [Amim] Cl was filtered through a granulated gel, [Bmim] Cl in yellowish powder, [Omim] Cl [C2mm] (MeO) ₂ PO ₂ was obtained as a white powder in a sticky gel state pressed on the bottom of silver.

Experimental Example 8

10 mL of distilled water was added to the solution of BKP dissolved in the ionic liquid, and the mixture was mixed well using Voltex with sufficient stirring and left for about 1 hour, depending on the type of ionic liquid, white matters subsided or existed in a turbid state. . C2mm] (MeO) ₂ PO ₂ was not dissolved in water but floated in water as a lump of gel.

The product was filtered through a glass filter, washed several times with water and acetone, and dried in a dryer to obtain a thin film.

III. Synthesis of Intermediate represented by Structural Formula 3 in Scheme 1

Preparation Example 1

[Reaction Scheme 2]

The same method as Experimental Example 3 35.9 ml of pyridine was added to a solution in which 7.3 g of cellulose was dissolved in 150 g of an ionic liquid. 35.4 ml of chloroacetyl chloride was added dropwise while cooling the mixture with ice water. The reaction mixture was stirred at room temperature for 4 days. When the compounds were separated in the same manner as in Experimental Example 7 and Experimental Example 8, the final product was identified by IR.

IV. Synthesis of Second Intermediate represented by Structural Formula 4 in Scheme 1

Production Example 2

Scheme 3

1.5 g of intermediate compound of Structural Formula 3 synthesized in Scheme 2 of Preparation Example 1 was slowly added with 25 ml of N, N'-dimethylacetamide, 0.266 g of potassium hydroxide and 0.577 g of 5,5, -dimethylhydantoin. After the solution was stirred at 90 ° C. for 24 hours, the precipitated material was filtered and dried to obtain a second intermediate compound of formula 4.

V. Synthesis of Compound of Structural Formula 1

≪ Example 1 >

[Reaction Scheme 4]

The intermediate compound (54 mmol) and 5.46 g triethylamine (54 mmol) represented by Structural Formula 3 in 21.25 g of Scheme 1 were mixed with 20 ml of n-hexane under a nitrogen atmosphere. The solution was stirred at rt for 24 h and then the precipitated material was filtered off. The remaining crystals were washed with n-hexane and the volatiles were removed under reduced pressure. Drying the solid product at room temperature yields Cell-TEACl, an intermediate compound of formula 3 wherein R ₁ , R ₂ , and R ₃ are ethyl groups in Scheme 1.

≪ Example 2 >

Scheme 5

1.25 g of Intermediate Compound (54 mmol) represented by Structural Formula 3 in Scheme 1 and 10.00 g of Tributylamine (54 mmol) were synthesized in the same manner as in Scheme 3 of Example 1, where R ₁ , R ₂ , and Cell-TBACl, an intermediate compound of formula 3, wherein R ₃ is a butyl group, is obtained.

≪ Example 3 >

[Reaction Scheme 6]

Synthesis of the intermediate compound (54 mmol) represented by Structural Formula 3 (21 mmol) and 13.24 g tributylamine (54 mmol) in 21.25 g of Scheme 1 in the same manner as in Scheme 3 of Example 1 showed R ₁ , R ₂ , and Cell-TPACl, an intermediate compound of formula 3, wherein R ₃ is a butyl group, is obtained.

<Example 4>

[Reaction Scheme 7]

21.25 g of Intermediate Compound (54 mmol) represented by Structural Formula 3 in Scheme 1 and 10.93 g of Tributylphosphine (54 mmol) were synthesized in the same manner as in Scheme 3 of Example 1, where R ₁ , R ₂ , And Cell-TBPCl which is an intermediate compound of Structural Formula 3 whose R <_3> is a butyl group is obtained.

&Lt; Example 5 &gt;

[Reaction Scheme 8]

Synthesis of the intermediate compound (54 mmol) represented by Structural Formula 3 (54 mmol) and 14.16 g of tributylamine (54 mmol) in 21.25 g of Scheme 1 in the same manner as in Scheme 3 of Example 1 provided that R ₁ , R ₂ , and Cell-TPPCl, which is an intermediate compound of Formula 3, wherein R ₃ is a phenyl group is obtained.

&Lt; Example 6 &gt;

Scheme 9

The intermediate compound (3.8 mmol) represented by Structural Formula 4 in Scheme 1 of 2.54, 25 ml of N, N'-dimethylacetamide, 0.26 g of potassium hydroxide, and 0.58 g of 5,5-dimethylhydantoin were added slowly. After the mixture was stirred at 90 ° C. for 24 hours, the precipitate was filtered and dried to give the product Cell-chlorohydantoin.

Experimental Example 9 Evaluation of Antimicrobial Activity

The antimicrobial activity by the test piece was evaluated by the spread plate method (JIS Z 2801: 2002). In the spread plate method (JIS Z 2801: 2002), the control group used untreated specimens. Test pieces were prepared by extruding a mixture of polypropylene and 4 wt.% Of the antimicrobial agent. Strains for the test were Staphylococcus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria).

Table 1 shows the spread plate method (JIS Z 2801: 2002) for 4 wt.% Of the antimicrobial agents [Cell-TEACl, Cell-TBACl, Cell-TPACl, Cell-TBPCl, Cell-TPPCl, Cell-chlorohydantoin]. Results are shown. The specimens of the antimicrobial agent inoculated with Staphylococcus aureus ( Straphylococcusaureus ) and Escherichia coli ( Escherichiacoli as) showed antimicrobial activity. After 24 hours, the number of viable bacteria in the specimens was less than 10 and the reduction ratio was 99.9% or more.

Table 1. Antimicrobial Activity Test Using Spread Plate Method JIS Z 2801: 2002)

The present invention described above is not limited to the above-described embodiments and the accompanying drawings, and various substitutions, modifications, and changes are possible within the scope without departing from the technical spirit of the present invention. It will be evident to those who have knowledge of.

As described above, the present invention using the ionic liquid is a method of directly reacting in a completely dissolved state of cellulose, so that all of the remaining hydroxyl groups having no antibacterial activity can be substituted, thereby increasing the antimicrobial activity and the wood-based biomass. Various kinds of biological resources can be used as raw materials, which can reduce raw material costs. In addition, since the antimicrobial agent of the present invention is immobilized by introducing a functional group into the cellulose polymer, the antimicrobial agent may be used in many fields such as food processing, filtration, and medical devices with high antimicrobial activity and selectivity as well as reduced residual toxicity and longer lifespan. It is also expected to be used for many applications such as the apparel industry made of antibacterial fibers, disinfectants and preservatives.

Claims (3)

A method of preparing a compound represented by the following Structural Formula 1 with the following Structural Formula 3 and the following Structural Formula 11 or Structural Formula 12:
[Structural formula 1]

[Structural Formula 3]

[Structural Formula 11]
X (R ₁ ) (R ₂ ) (R ₃ )
[Formula 12]

[In Formula 1, 3, 11 and 12,
AM ₁ , AM ₂ , and AM ₃ are each independently -X ⁺ (R ₁ ) (R ₂ ) (R ₃ ) or

;
X is N or P;
R ₁ to R ₃ are independently of each other ethyl, butyl or phenyl;
R ₄ or R ₅ is methyl.] The method of claim 1,
Structural formula 3 is prepared by reacting 2-chloroacetyl chloride with cellulose represented by the following structural formula 2 in the presence of an ionic liquid.
[Structural formula 2]

The method of claim 2,
Ionic liquids include 1-allyl-3-methylimidazolinium chloride ([Amim] Cl, 1-allyl-3-methylimidazolium chloride), 1-methyl-3-octylimidazolinium chloride ([Omim] Cl, 1-methyl-3-octylimidazolium chloride), 1-butyl-3-methylimidazolium chloride ([Bmim] Cl, 1-butyl-3-methylimidazolium chloride) or 1-methyl-3-ethylimidazolinium dimethyl Phosphate ([C2mim] (MeO) ₂ PO ₂ , 1-methyl-3-ethylimidazolium dimethylphosphate).

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